Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin-binding protein-dependent reduction of ?-catenin.

ABSTRACT: Sucrose nonfermenting 1 (Snf1)-related kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase (AMPK); however, its function is not well characterized. We conducted a gene array to determine which genes are regulated by SNRK. The array demonstrated that SNRK overexpression increased the levels of genes involved in cell proliferation, including calcyclin-binding protein (CacyBP), a member of the ubiquitin ligase complex that targets nonphosphorylated ?-catenin for degradation. We confirmed that SNRK increased CacyBP mRNA and protein, and decreased ?-catenin protein in HCT116 and RKO colon cancer cells. Furthermore, SNRK inhibited colon cancer cell proliferation, and CacyBP down-regulation reversed the SNRK-mediated decrease in proliferation and ?-catenin. SNRK overexpression also decreased ?-catenin nuclear localization and target gene transcription, and ?-catenin down-regulation reversed the effects of SNRK knockdown on proliferation. SNRK transcript levels were reduced in human colon tumors compared to normal tissue by 35.82%, and stable knockdown of SNRK increased colon cancer cell tumorigenicity. Our results demonstrate that SNRK is down-regulated in colon cancer and inhibits colon cancer cell proliferation through CacyBP up-regulation and ?-catenin degradation, resulting in reduced proliferation signaling. These findings reveal a novel function for SNRK in the regulation of colon cancer cell proliferation and ?-catenin signaling.

SUBMITTER: Rines AK 

PROVIDER: S-EPMC3475258 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature